Human Vascular Smooth Muscle Cells Have at Least Two Distinct PDGF Receptors and Can Secrete PDGF-AA

Hosang, Markus; Rouge, Marianne

doi:10.1097/00005344-198906146-00007

Cited by 22 publications

(11 citation statements)

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“…Cultured VSMCs can return to a synthetic phenotype that can be accompanied by an increase in the production and secretion of PDGF-like mitogens as well as expression of different ratios of PDGF BB and AB receptors. 18 Human VSMCs express threefold more PDGF BB than PDGF AB receptors, 19 and thymidine incorporation responded well to PDGF BB but poorly to PDGF AA; however, Swiss 3T3 cells, with about an equal number of BB and AB receptors, responded equally well to both isoforms. These findings led us to hypothesize that the high mitogenic responsiveness to PDGF BB of hypertensive cells might be related to expression of distinct proportions of either the AB or BB receptor isoforms.…”

Section: Hypertension Vot 23 No 6 Part 2 June 1994mentioning

confidence: 99%

Cell growth and Na-K-Cl cotransport responses of vascular smooth muscle cells of Milan rats.

et al. 1994

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The present study examines the role of serum growth factors in the proliferative response and Na-K-Cl cotransport activity of vascular smooth muscle cells from Milan normotensive (MNS) and hypertensive (MHS) rats. Cells from thoracic aorta of both strains were cultured in 10% serum medium and made quiescent by 72 hours in 0.3% serum medium. MHS cells grown with 10% serum had a shorter population doubling time than MNS cells between passages 8 and 12 (13.8±1.7 versus 20.1±1.6 hours, P<.01, n=4). MHS cells also exhibited a higher response of thymidine incorporation into nucleic acid to serum, epidermal, and platelet-derived growth factor BB. In MHS cells epidermal (100 ng/mL) and platelet (50 ng/mL) growth factors increased thymidine incorporation 2-and 10-fold, respectively. In MNS cells epidermal factor did not induce a significant response, and that of platelet factor was twofold lower than in MHS cells. Binding curves revealed a higher number of receptors for platelet than epidermal growth factor in both strains and a similar number of both receptors in MHS and MNS cells. Quantitative immunoblots of these recep-V ascular smooth muscle cells (VSMCs) within the tunica media of adult arteries are in quiescent state of growth, with the cell cycle reversibly arrested in the Gi/G 0 phase. In rats, the replication rate is approximately 0.02%, but this slow growth rate can be altered by mechanical injury and the release of growth factors by platelets, monocytes, and endothelial cells. The initiation of the proliferative cycle and the rate of growth are controlled by autocrine and paracrine secretion of growth factors and the expression of these receptors.1 Platelet-derived growth factor (PDGF), isoform BB, is the most powerful mitogenic for the initiation of the proliferative cycle in VSMCs, 2 and it may play a role in the hyperplasia of the tunica media in hypertension. Stimulation of ion fluxes is among the earliest changes induced by growth factor addition to Go-arrested cells. Activation of Na + -H + exchange by several mitogens has been well characterized in various cell types, 3 and stimulation of Ca 2+ -Na + exchange by PDGF BB 4 and of Na-K-Cl cotransport by epidermal growth factor (EGF) has been reported in VSMCs 5 and fibroblasts.6 Previous investigations have shown thatFrom the Endocrine-Hypertension Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass (M.C., G.V.), and Departamento de Inmunologia Ginica y Reumatologia, Facultad de Medicina, Universidad Catolica de Chile, Santiago (G.S., E.W., A.G.).Correspondence to Mitzy Canessa, PhD, Endocrine-Hypertension Division, Brigham and Women's Hospital, 221 Longwood Ave, Boston, MA 02115. tor proteins confirmed the observation that the greater proliferation of MHS cells could not be related to a higher number of growth factor receptors. Cotransport activity (bumetanide-sensitive M Rb influx in nanomoles per milligram protein per 5 minutes) was found to be significantly higher in MHS cells (16±3, n=18) t...

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Section: Hypertension Vot 23 No 6 Part 2 June 1994mentioning

confidence: 99%

Cell growth and Na-K-Cl cotransport responses of vascular smooth muscle cells of Milan rats.

et al. 1994

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“…Binding assays were performed as described by Hosang and Rouge [23]. Confluent cultures of VSMC were incubated at 4 ° C with saturating concentrations of either 125I-labeled PDGF-AA (10 ng/ml) or -BB homodimers (15 ng/ml).…”

Section: Samration Binding Assays For Pdgf Ilomodimersmentioning

confidence: 99%

“…Confluent cultures of VSMC were incubated at 4 ° C with saturating concentrations of either 125I-labeled PDGF-AA (10 ng/ml) or -BB homodimers (15 ng/ml). Nonspecific binding was determined in the presence of excess cold ligand [23].…”

Section: Samration Binding Assays For Pdgf Ilomodimersmentioning

confidence: 99%

Morphogenic Effects of Endothelin-1 on Vascular Smooth Muscle Cells

Hahn

Regenass²,

Resink³

et al. 1993

J Vasc Res

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Endothelin-1 (ET-1), a vasoconstrictor peptide produced by endothelial and vascular smooth muscle cells (VSMC) might play a role in vascular remodelling. To investigate the proposed ‘mitogenic’ potential of ET-1, we examined the effects of chronic exposure of VSMC to ET-1 on cell cycle, growth/proliferation and differentiation under essentially mitogen-free culture conditions. Bulk cultures of thoracic aortic VSMC of spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rats, although exhibiting genetically determined differences in growth/proliferation (due to shortened Gl and G2 phases in SHR VSMC), respond in a similar manner to ET-1 exposure: long-term exposure (12-15 days) of VSMC from both sources to ET-1 in nonmitogenic medium did not promote cycling of cells. On the contrary, ET-1 attenuated the cycling of VSMC which had already cycled beyond the S phase. For cells which had not cycled beyond the S phase, ET-1 interrupted progression through the cell cycle at the late Gl/early S phase. The specific ability of SHR VSMC to grow in mitogen-free medium was abolished by ET-1 most likely via down-regulation of platelet-derived growth factor (PDGF)-α receptors. Subsequent to ET-1 exposure, VSMC expressed increased levels of mRNA and protein for smooth-muscle-specific α-actin. However, expression of smooth muscle α-actin did not predominate over β-actin as observed for adult contractile VSMC in vivo. The ET-1-induced expression of smooth-muscle-specific α-actin mRNA was dose dependent (EC₅₀ approx. 2 × 10^-9M), and α-actin protein expressed was associated with organized actin fibers.

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“…PDGF is a mitogen (Hosang and Rouge, 1989;Reilly and Broski, 1989) and chemoattractant (Grotendorst et al, 1981;Albini et al, 1988) into the intima of the vessel wall (reviewed in Schwartz et al, 1986;Ross, 1986). PDGF would be released into the vessel wall following platelet adherence and degranulation in vivo.…”

mentioning

confidence: 99%

“…PDGF would be released into the vessel wall following platelet adherence and degranulation in vivo. Also, endothelial cells (Barrett et al, 1984;Collins et al, 1987;Gay and Winkles, 19901, smooth muscle cells (Majesky et al, 1988;Sjolund et al, 1988;Hosang and Rouge, 1989), and activated blood monocytes (Martinet et al, 1986) in culture produce PDGF. RNA gel blot (Barrett and Benditt, 1988) and in situ (Wilcox et al, 1988) hybridization studies have demonstrated that PDGF mRNA is expressed by vascular cells in normal human vessels and in atherosclerotic plaques.…”

mentioning

confidence: 99%

The half‐lives of platelet‐derived growth factor A‐ and B‐chain mRNAS are similar in endothelial cells and unaffected by heparin‐binding growth factor‐1 or cycloheximide

Gay

Winkles

1991

Journal Cellular Physiology

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Platelet-derived growth factor (PDGF) is mitogenic and chemotactic for vascular smooth muscle cells cultured in vitro, and, thus, may play a role in the smooth muscle cell proliferation and migration that occurs during atherosclerotic lesion development. Two related PDGF polypeptides, designated as the A and B chains, form functionally active PDGF-AA, AB, or BB dimers. The PDGF A- and B-chain genes are both transcribed in human umbilical vein endothelial (HUVE) cells and their expression is regulated by cytokines, growth factors, endotoxin, and phorbol ester. We reported previously that the angiogenic polypeptide heparin-binding growth factor (HBGF)-1 induces PDGF A-chain gene expression, but does not affect PDGF B-chain gene expression. In this study, we determined whether mRNA stabilization contributed to this induction by measuring the half-life of PDGF A-chain mRNA in quiescent, HBGF-1-stimulated, and proliferating HUVE cells. PDGF A-chain mRNA levels increase when quiescent HUVE cells are treated with the protein synthesis inhibitor cycloheximide; therefore, the effect of cycloheximide on PDGF A-chain mRNA decay was also investigated. The half-life of PDGF A-chain transcripts in quiescent cells was approximately 2.4 h and neither HBGF-1 nor cycloheximide significantly altered this decay rate. We also estimated the half-life of PDGF B-chain mRNA under the three different growth conditions and in the absence or presence of cycloheximide. The half-life in quiescent cells was approximately 1.8 h and was unaffected by HBGF-1 or protein synthesis inhibition. Therefore, the PDGF mRNAs have similar decay rates in HUVE cells, even though the 3' untranslated region of B-chain transcripts, but not A-chain transcripts, contains AU-rich sequence motifs postulated to confer rapid turnover in vivo.

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Human Vascular Smooth Muscle Cells Have at Least Two Distinct PDGF Receptors and Can Secrete PDGF-AA

Cited by 22 publications

References 0 publications

Cell growth and Na-K-Cl cotransport responses of vascular smooth muscle cells of Milan rats.

Cell growth and Na-K-Cl cotransport responses of vascular smooth muscle cells of Milan rats.

Morphogenic Effects of Endothelin-1 on Vascular Smooth Muscle Cells

The half‐lives of platelet‐derived growth factor A‐ and B‐chain mRNAS are similar in endothelial cells and unaffected by heparin‐binding growth factor‐1 or cycloheximide

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